The overall objective of the current research effort is to study the interrelationship between the ability of the mammalian stomach to maintain electrical and pH gradients, reflux of upper intestinal chyme, and the development of gastric mucosal disease, specifically acute hemorrhagic gastritis, chronic atrophic gastritis, and chronic benign gastric ulcer. Recent studies indicate that the topical application of bile salts to normal gastric mucosa results in an increase in nutrient gastric mucosal blood flow, a circumstance not mediated by B adrenergic receptors. Furthermore, in both normal and bile salt treated mucosae, augmentation of gastric mucosal blood flow increases apparent gastric mucosal permeability to hydrogen ion ("back diffusion"). When, in the presence of acid, the normal blood flow response to topically applied bile salts is impaired, acute ulcerogenesis occurs, suggesting that lesion formation is a function of the concomitant presence of acid, bile salts, and ischemia. During the coming year the research effort will be directed toward attempting to determine (1) the influence of selectively mitigating either the ischemic or the "back diffusion" component of the model described, using isoproterenol and cholestyramine, respectively; (2) the influence of different forms of topical bile acids on ulcerogenesis, specifically a comparison between sodium taurocholate, sodium glycocholate, and cholic acid in acid and neutral solutions; (3) the influence of preexisting atrophic gastritis on bile induced damage and on ulcerogenesis in the gastric mucosa; and (4) the influence of chronic bile acid application on mucosal histology and function.